ABSTRACT ? ARTFL LEFFTDS Longitudinal FTLD: OVERALL SECTION Frontotemporal Lobar Degeneration (FTLD) is the overarching term for a group of neurodegenerative disorders that are believed to be caused by the accumulation of toxic protein aggregates in the CNS, most commonly comprised of one of two major proteins?microtubule associated protein tau and TAR DNA binding protein molecular weight 43 kDa. FTLD is at least as common as Alzheimer's disease (AD) in those under the age of 65. Due to the earlier age of onset and the rapid rate of decline, FTLD is thought to have an even greater impact on the lives of patients and families when compared to AD. At least 20% of all FTLD patients have a dominantly inherited familial disorder (f-FTLD), whereas the remaining patients have a sporadic FTLD syndrome (s-FTLD). The current Advancing Research and Treatment in Frontotemporal Degeneration (ARTFL; U54 NS092089) study enrolls and follows these s-FTLD patients. Approximately 50% of f-FTLD is the result of one of three common mutations: the microtubule associated protein tau (MAPT), progranulin (GRN), or chromosome 9 open reading frame 72 (C9orf72) genes. The current Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS; U01 AG045390) study enrolls and follows participants with a known family mutation, while ARTFL also enrolls those with strong family histories but no known mutation. The ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) protocol represents our plan to formalize the merger of the ARTFL and LEFFTDS studies to create an integrated North American research consortium to study FTLD. The ALLFTD program, as implemented through this U19 mechanism, will improve our infrastructure for comprehensive collection and sharing of data through creation of seven cores. We address the main goals recommended by the National Alzheimer's Project Act (NAPA) Steering Committee on the Alzheimer's Disease-Related Dementias (ADRD) focused on FTLD through these cores and two research projects. ALLFTD will support many additional projects that address both the clinical and neuroscientific goals recommended by NAPA ADRD by providing clinical data, scans and biological samples to the scientific community. While there are no effective treatments for any FTLD disorder, increasing numbers of new potential therapies are entering clinical trials. The ALLFTD program's commitment to supporting data collection and sharing with researchers worldwide will foster development of disease-modifying therapies for FTLD.